Addition compound of quinolines and barbituric acids and the process of



Patented Sept. 27, 1932 UNITED STATES PAENT o FicE FRITZ MIETZSCILOF ELBERFELD, GERMANY, ASSIGNOR TO WINTHROP CHEMICAL COM- PANY, INQ, OF NEW YORK, N. Y., A CORPORATION OF NEW YORK ADDITION COMPOUND OF QUINOLINES AND BARBITURIC ACIDS PRODUCING SAME {No Drawing. Application filed iebruary 26, 1929, Serial No. 342,937, and in Germany February 27, 1928.

The present invention relates to the manu facture of therapeutically".- valuable compounds of 5-di substituted-barblturlc acids with ethers of '6 S-dihydroxyquinoline, and

to the new products obtainablethereby.

More, particularly my inventlon relates-to compounds of the probable general ,formula or an-alkyl=group Mylnew products areobtainable 2 by ,double decomposition. in aqueous solution of;equimol e cular. quantities of an alkali metal salt of a. dlsubstituted barbltur c.

acid of the formula wherein R and R 'stand for alkylor aryl groups or for the radical of a hydroaromatic hydrocarbon, and a mineral acid salt of a 6 8- dihydroxy-quinoline ether of the formula a sandy powder.

In contradistinction to ordinary mixtures of the starting materials, these compounds are practically colorless, insoluble in water, of high melting point and nearly tasteless, while the barbituric acids alone are unpleasgenerally in the form of AND THE PROCESS OF into their components both by acids and by.

alkalies and readilyexert their action in the human organism. They combine the sleep producing action of the barbituric acids with the antipyretic'and antispasmodlc; properties" of the 6.8 dihydroxyquinoline ethers,and

' v are valuable anti-epileptic substances.

The invention is illustrated by the following examples, but is not restricted thereto:

EwampZe 1.254 grams-of the sodium salt of 5.5-phenyl-ethyl-barbituric acid are dissolved in one liter of cold water and added all at once while thoroughly stirring to a solution of 217 grams of 6.8-diethoxyquinoline in one liter of normal hydrochloric acid.

The intense yellow, at first clear, solution loses its color in a fewminutes during the stirring, becoming cloudy and separating the double compound in the form of a white, viscous mass. After about minutes, the supernatent water is poured olf, and the product is washed several times with Water. After treating with ligroin for 5 minutes at 40 (1, the residue crumbles into a sandy, almost colorless powder, which is filtered, washed with ligroin and finally dried in a drying oven. It contains about 52% of phenylethylbarbituric acid and 48% of diethoxyquinoline and possesses a melting point of 130 C.

On shaking the product for a prolonged time with 15% caustic soda and ether and separating the aqueous from the ethereal layer, the 6.8-diethoxyqu'inoline can be obtained from the ethereal layer by distillation and the crystals of the phenylethylbarbituric acid from the aqueous layer by careful acidification.

Ewample 2.236 grams of 5.5-cyclohexenyl-ethyl-barbituric acid are dissolved in 1000 com. of normal caustic soda and combined with a solution of 189 grams of 6.8-dimethoxyquinoline in 1000 ccm. of normalhydrochloric acid. The double. compound is isolated in the manner described in Example 1.

I claim: 5. As new products the compounds of the l. The process which comprises reacting probable general formula: with an alkali metal salt of a di-substituted barbituric acid of the general formula:

wherein B and R stand for substituents of wherein R and R stand for alkyl and R the group consisting of alkyl, aryl and the stands for aryl, said compounds being generradical of a hydroaromatic hydrocarbon, ally colorless, water-insoluble substances of upon an equimolecular quantity of a mineral high melting point and being valuable antiacid salt of a 6.8-dihydroxyquinoline ether epileptic substances.

of the general formula: veii'l 'kl L'LP'TLH." it. Ii'w: .1112? a eel-amass, a i a' melting point of b i a v luable antiepileptic v witnesses-tame a? 130 C. and

substance! -11 1' 7- The} process which comprises reacting "with an alkali metal salt of a di-substituted barbituric acid of the general formula:

(JO-NH t-$ wherein iRn-i tands for-an alkylugroupiandr g- 1 R :standsgionanfaryligroup;aipon anvequi a; molecular quantityofea mineralJacid-salt a e -f RN an y -g 6.8-dihydr0 inglin th f, th ne l' R stands for' the radical of a hydroaromatic formula, V "4;"fihydrocaabeirfiupon an equimole'cular quan- W 'tity'ofa-iniiieralacid'salt'of a 6.8-dihydroXy is zquiiibliiieethei' of the" general formula:

wherein R 'istands for an alkyl aqueous solution.

6. As a new product the compound of the r 3. The pr which pri s ng" wherein R stands for an alkyl group, in

with the sodium salt of 5.5 pl 1enyl-ethyl-baraqueous l ti bitul'ic ac p n equimolecular qu n y 8.;The process which comprises reacting 'l hy m ld saltvof Q-A h YYi with the sodium salt of 5.5-cyclohexenyln lgaqueous solutlonf fethylbarbituric acid upon an equimolecular :::quantity of the hydrochloric acid salt of 4. As new products the compounds the '9 v l l 6.8-dimethoxyquinoline in aqueous solution.

. o R 9. As new products the compounds of the 3 R1 O probable general formula:

R (JO-NH 55 O-NET v (I)RI 31 mmO w v I I R: I; "l wherein R and R stands for substituents of GO NH N the group consisting of alkyl, aryl an'd the i I radical'of a hydroaromatic hydrocarbon, one .m R stands for an alkyl group and the other R stands'for hydrogen'or analkyl. group,

wherein R and'R stand' for alkyl and R stands for the radical of a hydroaromatic hysaid compounds being generally colorless, drocarbon'asaid compounds being generally waterinsoluble substances of high melting I1 S Watermsoluble Substances of high point and being valuable antiepileptic subg'p d being Valuable p pas stances. tic'substances.

10. As a. new product the compound of the probable formula:

11-0 OONH H00 my hand.

FRITZ MIETZSCH. 

